{"id":"e767e8b0-b5c7-5507-9e52-048609499f92","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-pcsk9-transcription","predicate":"reduces","statement":"Berberine lowered HNF1A-dependent PCSK9 transcription; proteasome inhibition prevented this response.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"d60431c8-8532-5e29-a6d5-aec0e64de292","mechanism_event_label":"This route regulates a protein that controls LDL-receptor availability.","subject":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"object":{"id":"9435f04a-8d8a-5aac-ac6e-196d9c5adb2a","slug":"pcsk9-transcription","display_name":"PCSK9 transcription","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"d60431c8-8532-5e29-a6d5-aec0e64de292","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-pcsk9-transcription-event","event_type":"biochemical_relationship","label":"This route regulates a protein that controls LDL-receptor availability.","description":"Berberine lowered HNF1A-dependent PCSK9 transcription; proteasome inhibition prevented this response.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c9b0f8e4-4823-5067-a352-61b4c37cd11b","slug":"hnf1a","display_name":"Human hepatocyte nuclear factor 1 alpha / HNF1A","entity_type_key":"protein"},"role":"transcriptional_regulator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d192bc4c-4922-5f09-9b62-ac603de6aab5","slug":"pcsk9","display_name":"Human proprotein convertase subtilisin/kexin type 9 / PCSK9","entity_type_key":"protein"},"role":"gene_product","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"9435f04a-8d8a-5aac-ac6e-196d9c5adb2a","slug":"pcsk9-transcription","display_name":"PCSK9 transcription","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/berberine-research/25540198.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446\", \"start_char\": 0, \"end_char\": 1769, \"text_sha256\": \"08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Protein-turnover and proteasome-inhibitor experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Berberine, ubiquitin assays and proteasome inhibition","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"HNF1A protein turnover differs from HNF1A gene transcription. Proteasome inhibitors are experimental probes, not suggested combination treatment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Berberine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human HepG2 cells; separate mouse and hamster arms","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This route regulates a protein that controls LDL-receptor availability.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berberine-p25540198] Inhibition of PCSK9 transcription by berberine involves down-regulation of hepatic HNF1α protein expression through the ubiquitin-proteasome degradation pathway. (2015). https://pubmed.ncbi.nlm.nih.gov/25540198/ DOI: 10.1074/jbc.m114.597229","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HNF1A and PCSK9 gene regulation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"9ef9a83a-d3f8-5496-aaa8-200df6387657","evidence_kind":"source_excerpt","locator":"Lines 480-491","start_line":480,"end_line":491,"excerpt":"### berberine-pcsk9-transcription\nBerberine lowered HNF1A-dependent PCSK9 transcription; proteasome inhibition prevented this response.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This route regulates a protein that controls LDL-receptor availability.\norganism: Human HepG2 cells; separate mouse and hamster arms\ntissue_or_cell_type: HNF1A and PCSK9 gene regulation\nexperimental_model: Protein-turnover and proteasome-inhibitor experiments\nlimitations: HNF1A protein turnover differs from HNF1A gene transcription. Proteasome inhibitors are experimental probes, not suggested combination treatment.\nexposure: Berberine, ubiquitin assays and proteasome inhibition\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/25540198.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446\", \"start_char\": 0, \"end_char\": 1769, \"text_sha256\": \"08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446\"}\n[berberine-p25540198] Inhibition of PCSK9 transcription by berberine involves down-regulation of hepatic HNF1α protein expression through the ubiquitin-proteasome degradation pathway. 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